DESCRIPTION (Adapted from the Application) This is a program directed at investigating the regulation and function of genes key for glucose homeostasis. Genes expressed in the liver and/or endocrine pancreas that encode important enzymes, hormones, and transcription factors will be emphasized. All of the products of these genes are of relevance to the etiology of NIDDM: the glucokinase and hexokinase II genes, the insulin gene, and phosphoenolpyruvate carboxykinase (PEPCK) gene. Exciting new investigations are proposed for a pancreas-duodenal homeodomain gene termed PDX-l, (also known as Idx-1, STF-l and IPF-l) that holds promise for providing insights into the molecular mechanisms of pancreatic development. The projects involve a group of investigators with related interests and skills so as to stimulate frequent collaborative interactions.